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免疫检查点阻断与非小细胞肺癌临床应答的生物标志物。

Immune checkpoint blockade and biomarkers of clinical response in non-small cell lung cancer.

机构信息

Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.

出版信息

Scand J Immunol. 2020 Dec;92(6):e12980. doi: 10.1111/sji.12980. Epub 2020 Oct 24.

Abstract

Immunotherapy with PD-1 and PD-L1 inhibitors has revolutionized the treatment for patients with NSCLC the last years with increased overall survival and in particular increased number of long-time survivors in patients with metastatic disease. It is now a treatment of choice for patients with distant metastases (stage IV) and in conjunction with chemoradiotherapy for patients with limited spread confined to the chest (stage III). PD-1 inhibition has been proven to be superior to standard chemotherapy, both as a single treatment and when combined with either chemotherapy or CTLA-4 inhibition. Despite the success of immunotherapy, the majority of patients do not respond or relapse within a short time frame. Biomarkers that would help to properly select patients with a high likelihood of clinical response to PD-1 and PD-L1 inhibitors are scarce and far from optimal, and only one (PD-L1 expression) has reached clinical practice. Thus for immunotherapy to be effective, the discovery and validation of additional biomarkers is critical for patient selection and prediction of clinical response. In this mini-review, we give an overview of current clinical management of NSCLC including treatment landscape with regard to immunotherapy, as well as discuss the current genetic and immune cell biomarker studies and their potential for introduction into clinical practice.

摘要

免疫疗法联合 PD-1 和 PD-L1 抑制剂在过去几年中彻底改变了非小细胞肺癌(NSCLC)患者的治疗方法,提高了总体生存率,特别是使转移性疾病患者的长期生存人数增加。目前,免疫疗法已成为远处转移(IV 期)患者的治疗选择,并与化疗和放疗联合用于局限于胸部的局限性疾病(III 期)患者。PD-1 抑制剂在单药治疗和联合化疗或 CTLA-4 抑制剂治疗方面均优于标准化疗。尽管免疫疗法取得了成功,但大多数患者在短时间内仍无法响应或复发。有助于正确选择对 PD-1 和 PD-L1 抑制剂有高度临床反应可能性的患者的生物标志物稀缺且远非最佳,只有一种(PD-L1 表达)已应用于临床实践。因此,为了使免疫疗法有效,发现和验证额外的生物标志物对于患者选择和预测临床反应至关重要。在这个迷你综述中,我们概述了 NSCLC 的当前临床管理,包括免疫疗法方面的治疗现状,并讨论了当前的遗传和免疫细胞生物标志物研究及其在临床实践中的潜在应用。

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